A man of novelty-seeking character has greater preference to a new subject or a medicine that is untouched yet. So, he is apt to show strange or dangerous behavior such as an adventure or a crime and be an alcoholic or a compulsory shopper with ease. However, physiological or genetic mechanisms involved in such behavior have not been discovered, yet.
A strange subject or a new environment not only causes curiosity but also anxiety or fear of its potential danger (Bronson, G. W., Psychol. Bull. 69, 350-358, 1968; Marks, I., J. Child Psychol. Psychiatry 28, 667-697, 1987). According to TPQ (Tri-dimensional Character Questionnaires) classification by Dr. Cloninger, people having a novelty-seeking character feel anxiety or fear of a strange subject less than others (Cloninger, C. R., Psychiatr. Dev. 4, 167-226, 1986). They enjoy adventures, dislike fixed idea, and have interests on various subjects of in variety of fields (Cloninger, C. R., Psychiatr. Dev. 4, 167-226, 1986; Cloninger, C. R. et al., Psychol. Rep. 69, 1047-1057, 1991; Maggini, C. et al., Compr. Psychiatry 41, 426-431, 2000). Dr. Noble at UCLA reported in 1998 that certain alleles of dopamine receptors DRD2 and DRD4 were found in people who were especially fond of alcohol, tobacco, drugs and adventurous behavior such as sky diving, bungee jump, etc (Noble, E. P. et al., Am. J. Med. Genet. 81, 257-267, 1998). However, a mechanism of human brain related to preference to such dangerous or strange stimuli has still been in question. That is because a proper animal model for studies on novelty-seeking character has not been given and no target molecule but a dopamine receptor has been found.
Voltage-dependent calcium channels are involved in increasing intracellular calcium content by the activation of neurons (Tsien, R. W., Annu. Rev. Physiol. 45, 341-358, 1983), and are classified into high-voltage dependent channels and low-voltage dependent channels (Tsien, R. W. et al., Trends Neurosci. 18, 52-54, 1995). T-type calcium channel is a representative low-voltage dependent channel and has three subclasses of Cav3.1(α1G), 3.2(α1H) and 3.3(α1I) according to the genotype for α1 subunit (Perez-Reyes, E., Physiol. Rev. 83, 117-161, 2003). α1G calcium channel is involved in the production of burst firings of neurons in thalamus and its relevant pathological functions have just recently been disclosed (Kim, D. et al., Science 302, 117-119, 2003; Kim, D. et al., Neuron 31, 35-45, 2001).
According to the studies on mice deficient in α1G calcium channel along with other pharmacological reports, α1G calcium channel is involved in the generation of SWDs (spike-and-wave discharge) of absence epilepsy by receiving signals from GABAB receptor (Kim, D. et al., Neuron 31, 35-45, 2001), and the suppression of continuous pain signal during the transmission of sensory signal, which is a major function of thalamus (Kim, D. et al., Science 302, 117-119, 2003). However, the effect of lacking in α1G T-type calcium channel on the behavior of an individual has not been explained.
Thus, the present inventors have observed mice deficient in α1G T-type calcium channel in the aspects of behavioral science. As a result, the present inventors have discovered that α1G transgenic mice have novelty-seeking and alcohol preference, and have completed this invention by confirming that those transgenic mice can be effectively used for the development of a medicine and a therapeutic method for human nervous diseases by using the mice as a nervous disease model for human nervous diseases such as novelty-seeking character, alcoholism, emotion disorder by stress and irregularity of desire, etc.